Rat study sug­gests Al­ler­gan's failed an­ti­de­pres­sant ra­pastinel may work as opi­oid ad­dic­tion treat­ment

Last month, when Al­ler­gan’s $AGN once-tout­ed pipeline star ra­pastinel crashed and burned a slate of piv­otal de­pres­sion stud­ies, it looked like the ex­per­i­men­tal mod­u­la­tor of the NM­DA re­cep­tor would be shroud­ed in a cloak of in­vis­i­bil­i­ty — but re­searchers may have found a way to res­cue the ex­per­i­men­tal drug by re­pur­pos­ing it as a treat­ment for opi­oid de­pen­dence.

Ju­lia Fer­rante

In the Unit­ed States, the cri­sis of opi­oid abuse, mis­use and over­dose — from pre­scrip­tion painkillers, hero­in, and syn­thet­ic opi­oids such as fen­tanyl — has reached epi­dem­ic pro­por­tions, caus­ing 130 deaths every day, ac­cord­ing to NIH es­ti­mates. Once in with­draw­al, ad­dicts are left to cope with a myr­i­ad of symp­toms in­clud­ing anx­i­ety, ag­i­ta­tion, sleep prob­lems, mus­cle aches, run­ny nose, sweat­ing, nau­sea, vom­it­ing, di­ar­rhea and opi­oid crav­ings.

In or­der to man­age these of­ten de­bil­i­tat­ing symp­toms, with­draw­al is man­aged by sub­sti­tu­tion with a less pow­er­ful opi­oid, fol­lowed by grad­ual re­duc­tion or tran­si­tion to main­te­nance ther­a­py with FDA-ap­proved med­ica­tion-as­sist­ed treat­ment (MAT) drugs such as methadone, buprenor­phine or nal­trex­one, which can have un­pleas­ant and some­times dan­ger­ous side ef­fects and of­ten must be used for months to avoid re­lapse. Al­though the process of ta­per­ing opi­oid con­sump­tion and us­ing MAT to treat opi­oid ad­dic­tion is stan­dard-of-care, it sus­tains the brain changes that re­sult in ad­dic­tion in the first place, which can lead to re­lapse be­fore treat­ment is com­plet­ed, ac­cord­ing to re­searchers who eval­u­at­ed the use of ra­pastinel in opi­oid de­pen­dence.

The tri­al in rats test­ed the use of ra­pastinel ver­sus ke­t­a­mine — a com­mon­ly-used cat tran­quil­iz­er and par­ty drug known as Spe­cial K or Kit Kat — which has been pro­posed as an al­ter­na­tive, non-opi­oid treat­ment for opi­oid with­draw­al, but it has the po­ten­tial for abuse, in­duces a trance-like state and can cause hal­lu­ci­na­tions. In fact, J&J’s $JNJ ke­t­a­mine-based de­pres­sion drug Spra­va­to has al­ready won FDA ap­proval. Ra­pastinel binds to the same re­cep­tor as ke­t­a­mine but at a dif­fer­ent site, where it con­fers a milder ef­fect.

Cyn­thia Kuhn

The sci­en­tists first in­duced opi­oid de­pen­dence in male and fe­male ado­les­cent (be­tween 28 and 30 days old) Sprague-Daw­ley rats by in­ject­ing them with mor­phine in in­creas­ing dos­es twice a day for five days. On day six, rats were in­ject­ed with nalox­one and with­draw­al signs were quan­ti­fied. The rats were then giv­en ei­ther ke­t­a­mine in­jec­tions twice dai­ly (n=12), ra­pastinel in­jec­tions every oth­er day (n=14), or saline in­jec­tions (n=24). On day nine, when the rats were giv­en nalox­one to mea­sure with­draw­al signs, ra­pastinel-treat­ed rats ex­hib­it­ed sig­nif­i­cant­ly few­er with­draw­al signs than those treat­ed with ke­t­a­mine.

The find­ings sug­gest that treat­ment with ra­pastinel in­duced safer with­draw­al, sans any se­ri­ous side ef­fects, dur­ing the crit­i­cal first days in the ef­fort to ab­stain from opi­oid use — and the sci­en­tists hy­poth­e­sized this would lead to a de­creased risk of opi­oid re­lapse.

“Ra­pastinel re­search for opi­oid de­pen­den­cy is cur­rent­ly on­ly be­ing done in ro­dents, but if the drug con­tin­ues to have suc­cess­ful tri­als, it may en­ter clin­i­cal tri­als for use in hu­mans,” said Ju­lia Fer­rante, an un­der­grad­u­ate at Vil­lano­va Uni­ver­si­ty who con­duct­ed the re­search with Cyn­thia Kuhn, pro­fes­sor of phar­ma­col­o­gy and can­cer bi­ol­o­gy at Duke Uni­ver­si­ty.

The re­searchers are look­ing to keep test­ing ra­pastinel to in­ves­ti­gate its ef­fect on the mol­e­c­u­lar lev­el and to check whether it can re­duce the risk of re­lapse. The drug has a long way to go be­fore it cross­es the fin­ish line, but if ap­proved it would like­ly be ad­min­is­tered in­tra­venous­ly, pos­si­bly in an out­pa­tient set­ting, Fer­rante added.

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.

Ted Love. HAVERFORD COLLEGE

Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Neil Woodford, Woodford Investment Management via YouTube

Un­der siege, in­vest­ment man­ag­er Wood­ford faces an­oth­er in­vest­ment shock

Em­bat­tled UK fund man­ag­er Neil Wood­ford — who has con­tro­ver­sial­ly blocked in­vestors from pulling out from his flag­ship fund to stem the blood­let­ting, af­ter a slew of dis­ap­point­ed in­vestors fled fol­low­ing a se­ries of sour bets — is now pay­ing the price for his ac­tions via an in­vestor ex­o­dus on an­oth­er fund.

Har­g­reaves Lans­down, which has in the past sold and pro­mot­ed the Wood­ford funds via its re­tail in­vest­ment plat­form, has re­port­ed­ly with­drawn £45 mil­lion — its en­tire po­si­tion — from the in­vest­ment man­ag­er’s In­come Fo­cus Fund.

Search­ing for the next block­buster to fol­low Darza­lex, J&J finds a $150M an­ti-CD38 drug from part­ner Gen­mab

Now that J&J and Genmab have thrust Darzalex onto the regulatory orbit for first-line use in multiple myeloma, the partners are lining up a deal for a next-gen follow-on to the leading CD38 drug.


Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.


Genmab is footing the bill on studies in multiple myeloma and diffuse large B-cell lymphoma; once it completes clinical proof of concept, Janssen has the option to license the drug for a $150 million exercise fee. There’s also $125 million worth of milestones in play.

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Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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Savara shares are crushed as PhI­II tri­al flunks pri­ma­ry, key sec­on­daries — but they can’t stop be­liev­ing

In­vestors are in no mood to hear biotechs tout the suc­cess of a “key” sec­ondary end­point when the piv­otal Phase III flunks the pri­ma­ry goal. Just ask Savara. 

The Texas biotech $SVRA went look­ing for a sil­ver lin­ing as com­pa­ny ex­ecs blunt­ly con­ced­ed that Mol­gradex, an in­haled for­mu­la­tion of re­com­bi­nant hu­man gran­u­lo­cyte-macrophage colony-stim­u­lat­ing fac­tor (GM-CSF), failed to spur sig­nif­i­cant­ly im­proved treat­ment out­comes for pa­tients with a rare res­pi­ra­to­ry dis­ease called au­toim­mune pul­monary alve­o­lar pro­teinosis, or aPAP.

As an­oth­er an­tibi­otics biotech sinks in­to a cri­sis, warn­ings of a sec­tor ‘col­lapse’

Another antibiotics company is scrambling to survive today, forcing the company’s founding CEO to exit in a reorganization that eliminates its research capabilities as the survivors look to improve on minuscule sales of their newly approved treatment. And the news — on top of an alarming series of failures — spurred at least one figure in the field to warn of a looming collapse of the antimicrobial resistance research field.

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'We kept at it': Jef­frey Blue­stone plots late-stage come­back af­ter teplizum­ab shown to de­lay type 1 di­a­betes

Late-stage da­ta pre­sent­ed at the Amer­i­can Di­a­betes As­so­ci­a­tion an­nu­al meet­ing in 2010 pushed Eli Lil­ly to put a crimp on teplizum­ab as the phar­ma gi­ant found it un­able to re­set the clock on new­ly di­ag­nosed type 1 di­a­betes. At the same con­fer­ence but in dif­fer­ent hands nine years lat­er, the drug is mak­ing a crit­i­cal come­back by scor­ing suc­cess in an­oth­er niche: de­lay­ing the on­set of the dis­ease.

In a Phase II tri­al with 76 high-risk in­di­vid­u­als — rel­a­tives of pa­tients with type 1 di­a­betes who have di­a­betes-re­lat­ed au­toan­ti­bod­ies in their bod­ies — teplizum­ab al­most dou­bled the me­di­an time of di­ag­no­sis com­pared to place­bo (48.4 months ver­sus 24.4 months). The haz­ard ra­tio for di­ag­no­sis was 0.41 (p=0.006).